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MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 20:
Nonmalignant Lymphocyte Disorders
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Review
Lymphs originate primarily from bone marrow and thymus
Secondary organs include spleen, lymph nodes, tonsils, and Peyer’s patches in GI tract
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Review
3 general populations B- lymphs: 10-20 % T-lymphs: 60-80% NK: < 10%
Pluripotent Stem cell
Lymphocyte Stem cell
B-cell T-cell
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Characteristic Cell
Reactive lymphocyte - transformed or benign lymph Similar terms are transformed lymph, atypical lymph,
virocyte, immunoblast, plasmacytoid, Downey cell What causes them?
Once stimulated by infection or inflammatory condition, lymphs enter various stages of activation
Morphologically heterogeneous population presents signs of activation: Large irregular shape Cytoplasmic basophilia Vacuoles Azurophilic granules can be present and are thought
to contain pore-forming proteolytic enzymes and serine proteases with pro-apoptotic activity.
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Antigen-stimulated lymphocytes pg. 129
Reactive or Atypical: Atypical is widely used; however, connotes abnormal or malignant
Downey Cell: obsolete term for reactive lymph and immunoblasts Immunoblasts:
large cells with prominent nucleoli fine clear chromatin dark purple-blue cytoplasm preparing for or engaged in mitosis in response to stimulus
Plasmacytoid lymphs: daughters of B immunoblasts Eccentric nucleus with moderate amount of deep blue cytoplasm
Plasma Cell Fully differentiated B cell Eccentric nucleus with “cartwheel appearance” with large amount of
basophilic cytoplasm Perinuclear clearing (Golgi apparatus) Releases Ig
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Reactive Lymph Characterisitcs
Reactive Lymph Normal Lymph
Size 9-30 µm 8-12 µm
N:C ratio Decreased High
Cytoplasm AbundantColorless to dark blueAzurophilic granulesCan scallop the RBCs
ScantColorless to light blue
Nucleus Elongated, irregular Round
Chromatin Coarse to moderately fine
Coarse
Nucleoli Absent to distinct Absent
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Introduction
Majority of disorders affecting lymphocytes are acquired Hallmark: reactive lymphocytosis Reactive process
Congenital disorders Defect is found within lymphocytic system
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Introduction
Important to differentiate benign conditions associated with lymphocytosis from malignant lymphoproliferative disorders How?
Presence of heterogeneous reactive lymphs Positive serological test for antibodies against
infectious organisms Absence of anemia and thrombocytopenia All of above favor a benign diagnosis
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Lymphocytosis
Excess of lymphocytes in the blood. Absolute lymphocyte count (ALC) > 4.8 x 109 /L in adults Relative count > 35-45% Self-limited Reactive process is due to infection or inflammatory
conditions B and T cells involved Lymphocytes develop in response to antigenic stimulation.
They become “activated”
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Causes of Reactive Lymphocytosis Infectious mononucleosis (IM)
Caused by the Epstein-Barr Virus (EBV) which enters the body via saliva (“kissing disease”)
EBV Pathophysiology EBV attaches to B lymphs by receptor CD21 which causes it to
express the activation marker CD23 that stimulates B-lymphocyte growth factor.
The virus is incorporated into the lymph genome making the cell express viral proteins on the cell membrane and immortalizes the line of EBV-lymphs.
Activated cytotoxic T-lymphs are released to inhibit the activation and proliferation of EBV infected lymphs. These are the characteristic Reactive Lymphs.
Clinical symptoms Classic triad: fever, pharyngitis and lymphadenpathy Dysphagia (difficulty swallowing) General malaise Fatigue Spleen is enlarged and nodes are firm but not tender or warm
Generally seen in children and young adults (14-24 yrs old)
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Lab features of IM
CBC Relative lymphocytosis
Peaks at 2-3 weeks of infection, remains elevated for 2-8 weeks
Leukocyte count 12-25 x 109/L Peripheral smear
Reactive lymphocytes , historically referred to as a Downey cell with irregular cytoplasmic border, increased cytoplasm and dark blue edge around the periphery of the cytoplasm.
>20% reactive lymphs Serologic test
Heterophil antibody test (i.e Monospot)
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Causes of Reactive Lymphocytosis
Toxoplasmosis Infection with intracellular protozoan
Toxoplasma gondii Acquired infections in children and adults
due to ingestion of oocysts from cat feces or undercooked meat
Can be transmitted via placenta
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Causes of Reactive Lymphocytosis
Cytomegalovirus (CMV) Infection Belongs to herpes family Endemic worldwide Acquired through transfusions, sexual
contact and close contact Can be transmitted across placenta Poor prognosis for immunocompromised
individuals who contract virus
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Causes of Reactive Lymphocytosis
Infectious lymphocytosis Affects children Viruses include adenovirus, coxsackie A
and Bordetella pertussis Leukocytosis and lymphocytosis occur in
first week of illness then return to normal
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Lymphocytopenia
Absolute lymphocyte count< 1.0 x 109/L Causes
Decreased production or increased destruction of lymphocytes
Changes in lymphocyte circulation patterns Corticosteroid therapy Other unknown causes Refer to page 411, table 20-4
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Immune Deficiency Disorders
Impaired function of one or more of the components of the immune system: T, B, or NK lymphocytes
Body unable to mount an adaptive immune response
Can be acquired or congenital
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Acquired Deficiencies
Acquired immune deficiency syndrome (AIDS) Infection with a retrovirus, human
immunodeficiency virus type-1 (HIV-1) Transmission through sexual contact or
contact with blood and/or blood products Binds CD4 antigen on helper T
lymphocytes which results in cell lysis
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Congenital Deficiencies
Decrease in lymphocytes and impairment in either cell-mediated immunity (Tcells), humoral immunity(Bcells) or both
Lymphocytes appear normal on ps
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Congenital Deficiencies
Severe Combined immunodeficiency Syndrome Major qualitative immune defects involving both
humoral and cellular immune functions Fatal by 2 years if untreated by bone marrow
transplant or gene therapy
Wiskott-Aldrich Syndrome Patients have recurrent infections due to
immunodeficiency (decreased CD8 T-lymphs), thrombocytopenia and eczema